Functional heterogeneity in non-suicidal self-injury across psychiatric disorders: neural and psychosocial correlates

Non-suicidal self-injury (NSSI) is a common behavior among adolescents, particularly within psychiatric populations. While neurobiological and psychosocial risk factors have been extensively studied, the mechanisms underlying NSSI's heterogeneity remain unclear. This study investigated 304 hospitalized adolescents/young adults (16-25 years) with NSSI and comorbid psychiatric diagnoses (major depressive disorder [MDD], bipolar disorder [BD], eating disorders [ED]) using psychological assessments and resting-state fMRI data from 163 participants. Orthogonal projection non-negative matrix factorization of Ottawa Self-Injury Inventory responses identified two latent factors: self-related factor and social-related factor. The self-related factor correlated with amygdala-centered cortico-limbic emotional regulation networks and predominated in affective disorders (MDD/BD), while the social-related factor linked to frontoparietal cognitive control and frontotemporal social cognition networks, particularly in ED. Fuzzy C-means clustering revealed three NSSI functional subtypes, independent of diagnostic categories: self-subtype primarily driven by self-related functions, social-subtype influenced by both self-related and social-related functions with greater exposure to psychosocial risks, and non-specific subtype characterized by mixed motivations. No subtype was exclusively driven by social-related functions. The "self-social" dual-dimensional framework with distinct neural mechanisms demonstrated subtype-specific profiles in functional connectivity, psychosocial risk exposure, and clinical features. Self-related mechanisms primarily engaged emotional regulation circuits, whereas social-related mechanisms emphasize the role of psychosocial risk factors and cognitive-emotional circuits. These findings provide neural evidence for the functional heterogeneity of NSSI and highlight the need for personalized interventions. Treatments targeting emotion regulation may benefit all subtypes, individuals with prominent social-related motivations may additionally require interventions aimed at improving interpersonal functioning.